Smads are important intracellular effectors in signaling pathways of the transforming growth factor-beta (TGF-beta). Receptor-activated Smads combine with a common Smad4 to translocate into the nucleus where they cooperate with other transcription factors to activate or repress transcription. SMAD4 is an important tumor suppressor gene. Smad4 has been shown to be constitutively phosphorylated, but the kinase that performs this phosphorylation is unknown. In this study, Smad4 was identified to interact with Nemo-like kinase (NLK) by a yeast two-hybrid system, and this interaction was confirmed in vitro and in vivo. Furthermore, the linker sequence of Smad4 is sufficient for this specific interaction. NLK is a conserved Ser/Thr kinase. Using in vitro kinase assays, we identified that threonine 9 (Thr9) and Serine 138 (Ser138) within the N-terminal Mad homology1 (MH1) domain of Smad4 could be phosphorylated by NLK. Our research suggests that NLK may play a novel role in the regulatory of Smad4 through phosphorylation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s11010-009-0230-2 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
ERBB4 selectively amplifies TGF-β pro-metastatic responses.
Cell Rep
January 2025
MOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Center for Life Sciences, Shaoxing Institute, Zhejiang University, Shaoxing, Zhejiang 321000, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, China; The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, China. Electronic address:
Transforming growth factor β (TGF-β) is well known to play paradoxical roles in tumorigenesis as it has both growth-inhibitory and pro-metastatic effects. However, the underlying mechanisms of how TGF-β drives the opposing responses remain largely unknown. Here, we report that ERBB4, a member of the ERBB receptor tyrosine kinase family, specifically promotes TGF-β's metastatic response but not its anti-growth response.
View Article and Find Full Text PDFSMAD4 Regulates the Expression of LCK Affecting Chimeric Antigen Receptor-T Cells Proliferation Through PI3K/Akt Signaling Pathway.
J Cell Physiol
January 2025
Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
The proliferation of CAR-T cells was hindered and cannot play its killing function well in solid tumors. And yet the regulatory mechanism of CAR-T cell proliferation is not fully understood. Here, we showed that recombinant expression of CD19CAR in T cells significantly increased the basal activation level of CAR-T cells and LCK activation.
View Article and Find Full Text PDFDRD4 Interacts with TGF-β Receptors to Drive Colorectal Cancer Metastasis Independently of Dopamine Signaling Pathway.
Adv Sci (Weinh)
December 2024
Department of Pathology and Run Run Shaw Hospital, Research Unit of Intelligence Classifification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042), Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.
The functional and pharmacological significance of dopamine receptor D4 (DRD4) in psychiatric and neurological disorders is well elucidated. However, the roles of DRD4 in colorectal cancer (CRC) remain unclear. This study observes a significant upregulation of DRD4 expression in clinical samples, which is negatively correlated with patient prognosis.
View Article and Find Full Text PDFExploring the role of peripheral nerves in trauma-induced heterotopic ossification.
JBMR Plus
January 2025
University of Texas, Southwestern Medical Center, Dallas, TX 75080, United States.
Recent studies have linked pain and the resultant nociception-induced neural inflammation (NINI) to trauma-induced heterotopic ossification (THO). It is postulated that nociception at the injury site stimulates the transient receptor potential vanilloid-1 (the transient receptor potential cation channel subfamily V member 1) receptors on sensory nerves within the injured tissues resulting in the expression of neuroinflammatory peptides, substance P (SP), and calcitonin gene-related peptide (CGRP). Additionally, BMP-2 released from fractured bones and soft tissue injury also selectively activates TRVP1 receptors, resulting in the release of SP and CGRP and causing neuroinflammation and degranulation of mast cells causing the breakdown the blood-nerve barrier (BNB), leading to release of neural crest derived progenitor cells (NCDPCs) into the injured tissue.
View Article and Find Full Text PDFOocyte-derived growth differentiation factor 9 suppresses the expression of CYP17A1 and androgen production in human theca cells.
F S Sci
February 2024
Reproductive Medicine Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China. Electronic address:
Article Synopsis
- The study aimed to explore how growth differentiation factor 9 (GDF9) affects androgen production in theca cells, which are related to ovarian function.
- Researchers treated cultured human theca cells with GDF9, an ALK5 inhibitor, and a SMAD4 agonist to observe changes in gene expression related to androgen synthesis and related signaling pathways.
- The results showed that GDF9 reduced the expression of key genes involved in androgen production and activated specific signaling pathways, indicating its role in suppressing androgen production in these cells.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!